Table 3 Compilation of the most important results of GLP-1 and GLP-1R agonists from human studies mentioned in the text

Decreases gastrointestinal motility extending the entry of nutrients to be absorbed by the GIT

[18]

mRNA transcripts were demonstrated in the human heart.

[31]

Normalizes postprandial glucose elevations by decreasing TGI motility, which seems to be more important than its insulinotropic effects.

[19]

Induces a mean increase in HR in patients with T2D.

[77]

Improves endothelial function expressed by an increase in flow-mediated vasodilation of the brachial artery, independent of changes in systolic and diastolic blood pressure during a hyperinsulinemic clamp in patients with T2D with stable CAD.

[36]

Increases endothelial nitric oxide synthase phosphorylation and nitric oxide production by the AMPK-dependent pathway in cultured Human Coronary Artery Endothelial Cells.

[56],[57]

Increases myocardial glucose uptake under basal conditions in lean humans, but this effect was impaired in T2D.

[47]

With metformin ameliorates high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells.

[59]

improves global and regional LV wall motion scores reducing stay and in-hospital mortality of patients with LV dysfunction after myocardial infarction.

[50],[51]

Increases endogenous antioxidant defenses, inhibits of cardiomyocyte apoptosis, attenuates of endothelial inflammation and dysfunction.

[62]

Protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism.

[58]

Reduces in 19% the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) and in 12% cardiovascular hospitalizations.

[71]

Enhances acetylcholine-induced forearm blood flow.

[61]

Reduces pulmonary capillary wedge pressure and increased both inotropism and chronotropism. In T2D patients with chronic heart failure.

[73]

Human studies

Increases muscle sympathetic nerve activity without affecting BP, norepinephrine plasma concentration, or the sympathetic/parasympathetic balance, where sympathetic drive is at least partially compensated by an increase in the parasympathetic activity

[62]

Reductes infarct size and improves subclinical LV function when added to primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction.

[14]

May have renoprotective function by significantly increased excretion of sodium, calcium, and chloride and significantly decreased excretion of H + in obese patient.

[63]

When administered once in a week assistes more patients in reaching the majority of ADA-recommended therapeutic goals than treatment with sitagliptin, pioglitazone, or insulin glargine as shown by clinical trials.

Concentration in human plasma is found to be positively associated with total coronary plaque load.

[66]

When administered once in a week elicites a greater response than does short-acting exenatide once a day, improving glycemic and lipids controls, lipoprotein metabolism, and decreasing systemic inflammation.

Improves LVEF, myocardial ventilation oxygen consumption, 6-min walk distance, and quality of life. In both diabetic and non-diabetic patients presenting class II/IV heart failure

[78]

Achieves better glycemic control and comparable hemodynamic recovery without the requirements for high-dose insulin or inotropes when infused perioperatively in patients with CAD and preserved LV function scheduled to undergo coronary artery bypass grafting. There were also more frequent arrhythmias requiring anti-arrhythmic agents in the control group.

[79]

Treatment is safe and elicites a significant improvement LVEF in patients with acute MI and LVEF <40% after successful primary angioplasty when compared with control.

[74]

Protects the heart from ischemic LV dysfunction induced by dobutamine stress in patients with CAD.

[75]